The study of high frequency/low penetrance genes and how they affect mutation rates of oncogenes and tumor suppressor genes is an exciting area of investigation. The goal of Research Core 2 is to foster and support research into the complex gene/environment interactions that define individual cancer risk, particularly as it relates to genetic polymorphisms that affect penetrance of tumor suppressor gene mutations. This will be accomplished by a three pronged approach to interdisciplinary research. The first is to support basic studies of molecular and genetic mechanisms of carcinogenesis among the laboratory-based investigators; the second will be in the area of basic epidemiology; and the third will be the interface of molecular and epidemiologic studies. Specifically, studies will be conducted to evaluate mechanisms of carcinogen action, mutagenic and epigenetic mechanisms in multistage carcinogenesis, identification, cloning, and functional characterization of cancer susceptibility genes and oncogenes, exposure assessment, epidemiological studies of cancer risk factors, genetic and environmental modifiers of cancer risk, and cancer prevention studies.